Importance of a syndapin-mediated interconnection of cytoskeleton and membrane trafficking for neuronal structure, function and plasticity

Syndapin 介导的细胞骨架和膜运输互连对神经元结构、功能和可塑性的重要性

• 批准号: 65984042
• 负责人: Professorin Dr. Britta Qualmann
• 金额: --
• 依托单位: Institut für Biochemie I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/65984042?language=en
• 关键词: Importance; syndapin; mediated; interconnection; cytoskeleton

Postsynaptic plasticity mechanisms are considered to be the structural basis of learning and memory. To meet the requirements of growth, adaptation and plasticity of the brain, dynamic adaptations reflected in changes in number, morphology and reorganization of synaptic contacts in response to diverse stimuli are indispensable. At the molecular level, these processes in postsynaptic specializations are characterized by the modulation of the plasma membrane levels of AMPA-type glutamate receptors and by dynamics of the actin cytoskeleton. A coordination of structural reorganizations including formation, maturation and plastic restructuring of synapses with a modulation of the activatable AMPA-receptor proportion through regulation of receptor endocytosis and recycling by molecular links of these processes provides an attractive unifying mechanism for activity-dependent synapse modification. Our previous analyses in non-neuronal cells have demonstrated that syndapins play an essential role in actin cytoskeletal dynamics, receptor-mediated endocytosis and endosomal recycling of membrane receptors and furthermore ensure functional interconnections between these different cellular functions. The morphological and functional characterization of the inducible knockout mice of the mainly neuronal syndapin I isoform that we have established shall unravel the role of this coordinator protein in the structural organization and dynamics of postsynaptic morphology as well as in receptor membrane trafficking processes. Analyses in the course of this project at the whole animal level, in functional brain sections and in primary cell culture systems shall reveal how syndapin I-mediated interconnections of actin dynamics, specialized cytomatrix components of the postsynaptic density, receptor-mediated endocytosis and endosomal receptor recycling overtake coordinative functions that are crucial for the formation, maturation, preservation, function and plastic modulation of postsynaptic nerve endings and thus underlie neuronal plasticity.

突触后可塑性机制被认为是学习和记忆的结构基础。为了满足大脑的生长、适应和可塑性的要求，突触接触的数量、形态和重组等动态适应在不同刺激下的变化是必不可少的。在分子水平上，这些突触后特化过程的特征是ampa型谷氨酸受体的质膜水平的调节和肌动蛋白细胞骨架的动力学。结构重组包括突触的形成、成熟和可塑性重组，通过调节受体内吞作用和这些过程的分子链接来调节可活化的ampa受体比例，为活性依赖性突触修饰提供了一个有吸引力的统一机制。我们之前对非神经元细胞的分析表明，syndapins在肌动蛋白细胞骨架动力学、受体介导的内吞作用和膜受体的内体再循环中发挥重要作用，并进一步确保这些不同细胞功能之间的功能互联。我们已经建立的主要神经元突触蛋白I异构体的诱导敲除小鼠的形态和功能特征将揭示这种协调蛋白在突触后形态的结构组织和动力学以及受体膜运输过程中的作用。本项目在全动物水平、功能性脑切片和原代细胞培养系统中进行的分析将揭示突触蛋白i介导的肌动蛋白动力学相互连接、突触后密度的特殊细胞基质成分、受体介导的内吞作用和内体受体再循环如何超越对细胞的形成、成熟、保存、突触后神经末梢的功能和可塑性调节，因此是神经元可塑性的基础。

项目成果

Cooperative functions of the two F-BAR proteins Cip4 and Nostrin in the regulation of E-cadherin in epithelial morphogenesis

两种 F-BAR 蛋白 Cip4 和 Nostrin 在上皮形态发生中 E-钙粘蛋白调节中的协同功能

• DOI: 10.1242/jcs.155929
• 发表时间: 2015
• 期刊: Journal of Cell Science
• 影响因子: 4
• 作者: Zobel T;Brinkmann K;Koch N;Schneider K;Seemann E;Fleige A;Qualmann B;Kessels MM;Bogdan S
• 通讯作者: Bogdan S

Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin I

• DOI: 10.1038/emboj.2011.339
• 发表时间: 2011-12-14
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Koch, Dennis;Spiwoks-Becker, Isabella;Qualmann, Britta
• 通讯作者: Qualmann, Britta

F-BAR Proteins of the Syndapin Family Shape the Plasma Membrane and Are Crucial for Neuromorphogenesis

• DOI: 10.1523/jneurosci.3973-09.2009
• 发表时间: 2009-10-21
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Dharmalingam, Elavarasi;Haeckel, Akvile;Qualmann, Britta
• 通讯作者: Qualmann, Britta